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Brassica vegetables contain glucosinolates and S-methyl-l-cysteine sulfoxide, which can be enzymatically hydrolyzed to form bioactive compounds. Glucosinolate hydrolysis can result in formation of health-promoting isothiocyanates, however, often less desirable nitriles and epithionitriles are formed due to presence of specifier proteins. Also, S-methyl-l-cysteine sulfoxide yields beneficial volatile organosulfur compounds (VOSC), such as S-methyl methanethiosulfinate. To optimize the nutritional value of Brassica oleracea vegetables, the outcome of these hydrolysis pathways was monitored over the harvest seasons of different cultivars in three consecutive years. Strong seasonal shifts in glucosinolate hydrolysis were observed only in red cabbages. They formed up to 40-fold more isothiocyanates in summer than in autumn, when nitriles and epithionitriles increased due to the induction of epithiospecifier proteins. Further, higher VOSC levels were found in autumn red cabbage. By elucidating the impact of abiotic growth factors on the regulation of the hydrolyses, the health value of Brassica vegetables can be improved., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Franziska Sabine Hanschen reports financial support was provided by Leibniz Association. Vanda Púčiková reports financial support was provided by Leibniz Association. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

γ-l-Glutamyl-S-allyl-l-cysteine (GSAC) is renowned for its flavor-modifying effects and beneficial biological activities. However, the level of GSAC decreases significantly during the processing of black garlic, and the pathways and degradation products resulting from this decline remain unclear. To investigate the potential transformation mechanisms of GSAC in black garlic, simulation systems for thermal decomposition, Maillard reactions, and enzymatic hydrolysis were established. In addition to GSAC and fructose, a total of 6 products were identified and confirmed. Findings indicate that thermal decomposition and enzymatic hydrolysis are the two primary pathways through which GSAC is transformed, whereas the Maillard reaction between fructose and GSAC is unlikely to occur. GSAC can be converted into S-allylcysteine and glutamic acid through thermal processing and the action of γ-glutamyl transpeptidase. Notably, the majority of Glu transformed into pyroglutamic acid via intramolecular dehydration at 75 °C, whereas in enzymatic hydrolysis simulation systems, it is converted into glutamine. Additionally, alliin, S-allylcysteine, and S-allylmercaptocysteine were detected, suggesting new pathways for the production of these compounds during the processing of black garlic.

Ischemic heart disease is the main global cause of death in the world. Abnormal sulfide catabolism, especially hydrogen sulfide accumulation, impedes mitochondrial respiration and worsens the prognosis after ischemic insults, but the substantial therapeutic strategy has not been established. Non-thermal atmospheric pressure plasma irradiation therapy is attracted attention as it exerts beneficial effects by producing various reactive molecular species. Growing evidence has suggested that supersulfides, formed by catenation of sulfur atoms, contribute to various biological processes involving electron transfer in cells. Here, we report that non-thermal plasma-irradiated cysteine (Cys∗) protects mouse hearts against ischemia/reperfusion (I/R) injury by preventing supersulfide catabolism. Cys∗ has a weak but long-lasting supersulfide activity, and the treatment of rat cardiomyocytes with Cys∗ prevents mitochondrial dysfunction after hypoxic stress. Cys∗ increases sulfide-quinone oxidoreductase (SQOR), and silencing SQOR abolishes Cys∗-induced supersulfide formation and cytoprotection. Local administration of mouse hearts with Cys∗ significantly reduces infarct size with preserving supersulfide levels after I/R. These results suggest that maintaining supersulfide formation through SQOR underlies cardioprotection by Cys∗ against I/R injury., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The variations in alliin content are a crucial criterion for evaluating garlic quality and is the sole precursor for allicin biosynthesis, which is significant for the growth, development, and stress response of garlic. WRKY transcription factors are essential for enhancing stress resistance by regulating the synthesis of plant secondary metabolites. However, the molecular mechanisms regulating alliin biosynthesis remain unexplored. Here, we report for the first time that a WRKY family transcription factor regulates the expression of a key enzyme gene in the alliin biosynthesis pathway, enhancing the accumulation of alliin., Results: AsWRKY9 was most highly expressed in garlic leaves, and its expression was significantly upregulated at various time points following leaf injury. Moreover, we established an improved garlic callus induction medium based on MS medium with 1.5 mg/L 2,4-D and 0.5 mg/L NAA, suitable for "PiZi" garlic bulbils. In transgenic callus overexpressing AsWRKY9, the transcription level of the key enzyme flavin-containing monooxygenase gene (AsFMO1) significantly higher, as did its enzymatic activity compared with the control. Subcellular localization revealed that AsWRKY9 is located in the nucleus. The promoter sequence of AsFMO1 was then obtained using genomee walking. Yeast one-hybrid (Y1H) and dual-luciferase assays (LUC) confirmed that AsWRKY9 interact with the AsFMO1 promoter. Further verification by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation qPCR (ChIP-qPCR) confirmed that AsWRKY9 interacts by binding to the W-box site on the AsFMO1 promoter. Compared to the control, the alliin content in the transgenic callus overexpressing AsWRKY9 was significantly increased, thus confirming the activation of the alliin biosynthesis pathway and enhancing the accumulation of alliin in garlic., Conclusions: Our study reveals the crucial role of AsWRKY9 in alliin biosynthesis, filling a gap in the complex transcriptional regulation of the alliin biosynthetic pathway. It provides a new molecular breeding strategy for developing garlic varieties with high alliin content., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Cats with progressive renal diseases often exhibit a weakened urinary odor, in contrast to normal cat urine which emits odorants with catty odor, such as 3-mercapto-3-methyl-1-butanol, 3-mercapto-3-methylbutyl formate, 3-methyl-3-methylthio-1-butanol, and 3-methyl-3-(2-methyldisulfanyl)-1-butanol. Felinine, an amino acid, is a precursor of these odorants and metabolized from its precursor, 3-methylbutanol glutathione (MBG), via 3-methylbutanol-cysteinylglycine (MBCG). While previous studies have reported felinine excretion in normal cats, its levels in cats with renal diseases remain unclear. This study investigates the urinary excretion of felinine and its precursors in cats with renal diseases and explores whether changes in these metabolites are linked to reduced volatile felinine derivatives with catty odor. Liquid chromatography/mass spectrometry quantified urinary felinine, MBCG, and MBG in 40 normal cats and 66 cats with renal diseases (classified into mild, moderate, and severe renal diseases), revealing a significant decrease in urinary felinine levels in cats with advanced renal disease, while urinary MBG levels increased. The felinine-to-MBG ratio was significantly lower in cats with severe renal disease compared to normal cats and those with mild renal disease. Gas chromatography/mass spectrometry analysis further showed that the emission of felinine derivatives decreased markedly with renal disease progression. A significant correlation was found between urinary felinine excretion and its major derivative, 3-methyl-3-methylthio-1-butanol. These findings suggest that impaired felinine metabolism, likely due to reduced kidney enzyme activity, contributes to both diminished urinary felinine levels and reduced sulfurous odor in cats with renal diseases.

Higher intakes of cruciferous and allium vegetables are associated with a lower risk of cardiometabolic-related outcomes in observational studies. Whilst acknowledging the many healthy compounds within these vegetables, animal studies indicate that some of these beneficial effects may be partially mediated by S-methyl cysteine sulfoxide (SMCSO), a sulfur-rich, non-protein, amino acid found almost exclusively within cruciferous and alliums. This scoping review explores evidence for SMCSO, its potential roles in human health and possible mechanistic action. After systematically searching several databases (EMBASE, MEDLINE, SCOPUS, CINAHL Plus Full Text, Agricultural Science), we identified 21 original research articles meeting our inclusion criteria. These were limited primarily to animal and in vitro models, with 14/21 (67%) indicating favorable anti-hyperglycemic, anti-hypercholesterolemic, and antioxidant properties. Potential mechanisms included increased bile acid and sterol excretion, altered glucose- and cholesterol-related enzymes, and improved hepatic and pancreatic β-cell function. Raising antioxidant defenses may help mitigate the oxidative damage observed in these pathologies. Anticancer and antibacterial effects were also explored, along with one steroidogenic study. SMCSO is frequently overlooked as a potential mediator to the benefits of sulfur-rich vegetables. More research into the health benefits of SMCSO, especially for cardiometabolic and inflammatory-based pathology, is warranted. Human studies are especially needed.

Quantitative monitoring of the concentrations of epigallocatechin gallate (EGCG) and cysteine (Cys) is of great significance for promoting human health. In this study, iron/aluminum bimetallic MOF material MIL-53 (Fe, Al) was rapidly prepared under room temperature using a co-precipitation method, followed by investigating the peroxidase-like (POD-like) activity of MIL-53(Fe, Al) using 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic substrate. The results showed that the Michaelis -Menten constants of TMB and H 2 O 2 as substrates were 0.167 mM and 0.108 mM, respectively. A colorimetric sensing platform for detecting EGCG and Cys was developed and successfully applied for analysis and quantitative detection using a smartphone. The linear detection range for EGCG was 15∼80 μM (R 2 =0.994) and for Cys was 7∼95 μM (R 2 =0.998). The limits of detection (LOD) were 0.719 μM and 0.363 μM for EGCG and Cys, respectively. This work provides a new and cost-effective approach for the real-time analysis of catechins and amino acids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The bioluminescence reaction of firefly luciferase with D-luciferin has become an indispensable imaging technique in modern biology and life science experiments, but the high cost of D-luciferin is limiting its further application. Here, we report a practical, one-pot synthesis of D-luciferin from p-benzoquinone (p-BQ), L-cysteine methyl ester and D-cysteine, with an overall yield of 46%. Our route, which is six steps in length and proceeds via 2-cyano-6-hydroxybenzothiazole, is inspired by the mechanistic study of our previously reported biomimetic, non-enzymatic, one-pot formation of L-luciferin from p-BQ and L-cysteine. Advantages of our route include its high yield, low cost, use of only inexpensive, commercially available reagents, without requiring strictly anhydrous and oxygen-free conditions, and elevated temperatures., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Plant fertility is fundamental to plant survival and requires the coordinated interaction of developmental pathways and signaling molecules. Nitric oxide (NO) is a small, gaseous signaling molecule that plays crucial roles in plant fertility as well as other developmental processes and stress responses. NO influences biological processes through S-nitrosation, the posttranslational modification of protein cysteines to S-nitrosocysteine (R-SNO). NO homeostasis is controlled by S-nitrosoglutathione reductase (GSNOR), which reduces S-nitrosoglutathione (GSNO), the major form of NO in cells. GSNOR mutants (hot5-2/gsnor1) have defects in female gametophyte development along with elevated levels of reactive nitrogen species and R-SNOs. To better understand the fertility defects in hot5-2, we investigated the in vivo nitrosoproteome of Arabidopsis (Arabidopsis thaliana) floral tissues coupled with quantitative proteomics of pistils. To identify protein-SNOs, we used an organomercury-based method that involves direct reaction with S-nitrosocysteine, enabling specific identification of S-nitrosocysteine-containing peptides and S-nitrosated proteins. We identified 1,102 endogenously S-nitrosated proteins in floral tissues, of which 1,049 were unique to hot5-2. Among the identified proteins, 728 were novel S-nitrosation targets. Notably, specific UDP-glycosyltransferases and argonaute proteins are S-nitrosated in floral tissues and differentially regulated in pistils. We also discovered S-nitrosation of subunits of the 26S proteasome together with increased abundance of proteasomal components and enhanced trypsin-like proteasomal activity in hot5-2 pistils. Our data establish a method for nitrosoprotein detection in plants, expand knowledge of the plant S-nitrosoproteome, and suggest that nitro-oxidative modification and NO homeostasis are critical to protein quality control in reproductive tissues., Competing Interests: Conflict of interest statement. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Garlic ( Allium sativum L.) is a species of the onion family ( Alliaceae ) widely used as a food and a folk medicine. The objective of this study was to determine the effects of AGE (aged garlic extract) on pro-inflammatory genes relevant to COVID-19. To this aim, we treated bronchial epithelial IB3-1 cells with SARS-CoV-2 spike protein (S-protein) or with the COVID-19 BNT162b2 vaccine in the absence or in the presence of AGE. The results obtained demonstrated that AGE is a potent inhibitor of the S-protein-induced expression of the IL-1β, IL-6 and IL-8 genes. Bio-Plex analysis demonstrated that AGE reduced release of IL-6 and IL-8, which were highly induced by S-protein. No inhibition of cells' growth, toxicity and pro-apoptotic effects were found in AGE-treated cells. The effects of one of the major AGE constituents (S-allyl cysteine, SAC) were studied on the same experimental model systems. SAC was able to inhibit the S-protein-induced expression of IL-1β, IL-6 and IL-8 genes and extracellular release of IL-6 and IL-8, confirming that S-allyl-cysteine is one of the constituents of AGE that is responsible for inhibiting S-protein-induced pro-inflammatory genes. Docking experiments suggest that a possible mechanism of action of SAC is an interference with the activity of Toll-like receptors (TLRs), particularly TLR4, thereby inhibiting NF-κB- and NF-κB-regulated genes, such as IL-1β, IL-6 and IL-8 genes. These results suggest that both AGE and SAC deserve further experimental efforts to verify their effects on pro-inflammatory genes in SARS-CoV-2-infected cells.

Objective: To describe the use of nuclear medicine cerebral perfusion studies as an ancillary test for brain death/death by neurologic criteria (BD/DNC) in infants aged under 1 year., Design: Retrospective case series., Setting: Single-center, quaternary, academic children's hospital in the United States., Patients: Patients younger than 1 year of age whose evaluation for BD/DNC included a nuclear medicine cerebral perfusion study as an ancillary test, 2005-2022., Interventions: None., Measurements and Main Results: Ten infants were identified from local databases. Mechanisms of brain injury included hypoxic-ischemic injury (8/10), traumatic brain injury (1/10), and intracranial hemorrhage (1/10). Testable components of the first BD/DNC examination were consistent with BD/DNC in all patients. Apnea testing was consistent with BD/DNC in 5 of 10 patients and deferred or terminated prematurely in 5 of 10 patients. All patients underwent ancillary testing with a nuclear medicine scan to assess cerebral perfusion using 99mTc-ethyl cysteinate dimer (99mTc-ECD). Indications were inability to complete the apnea test (5/10), presence of a confounder to the clinical examination (3/10), and clinician discretion (2/10). Nine studies were consistent with BD/DNC. The patient whose ancillary test was inconsistent with BD/DNC had their examination limited by the inability to assess the pupillary reflex and subsequently underwent withdrawal of life-sustaining technology., Conclusions: Radionuclide cerebral perfusion studies using 99mTc-ECD were used in our setting to support the determination of BD/DNC in infants aged younger than 1 year of age., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Glucolipotoxicity (GLT) has emerged as established mechanism in the progression of diabetes. Identifying compounds that mitigate GLT-induced deleterious effect on β-cells are considered important strategy to overcome diabetes. Hence, in the present study, astaxanthin-s-allyl cysteine (AST-SAC) diester was studied against GLT in β-cells. Mus musculus pancreatic β-cell line (βTC-tet) was treated with high glucose (25 mM; HG) and 95 μM palmitate (PA) for 24 h to induce GLT. AST-SAC at various concentrations (5, 10, and 15 μg/ml) were treated to understand the protective effect against HG + PA exposure in β-cells. Under HG + PA exposure conditions oxidative stress, deregulation of mTOR pathway and endoplasmic reticulum (ER) stress are witnessed. AST-SAC treatment eased oxidative stress, mitochondrial depolarization, DNA damage, calcium overload and accumulation of autophagosome against HG + PA exposure conditions thereby protected the cell viability of β-cells. AST-SAC maintained the level of proteins involved in mTOR pathway under HG + PA exposure conditions. Also, AST-SAC treatment has mitigated the increased expression of genes and proteins such as IRE1 and PERK involved in ER stress-mediated unfolded protein response (UPR) signaling pathways. In correspondence to it, the expression of genes involved in insulin secretion was preserved by AST-SAC. Due to these protective effects of AST-SAC the insulin secretion was well-maintained in β-cells under HG + PA exposure conditions. AST-SAC through normalizing antioxidant status and mTOR axis as well as preventing the harmful effect of ER-stress mediated UPR pathway has promoted the β-cell survival and insulin secretion against GLT. Simultaneously targeting oxidative stress/mTOR axis/ER stress is required to efficiently overcome GLT in β-cells., (© 2024 Wiley Periodicals LLC.)

Intensive agricultural practices impact the health and nutrition of pollinators like honey bees ( Apis mellifera ). Rapeseed ( Brassica napus L.) is widely cultivated, providing diverse nutrients and phytochemicals, including S -methyl-L-cysteine sulfoxide (SMCSO). While the nutritional impact of rapeseed on bees is known, SMCSO's effects remain unexplored. We examined SMCSO and its related metabolites-3-methylthiolactic acid sulfoxide and N -acetyl -S -methyl-L-cysteine sulfoxide-analysing their seasonal fluctuations, colony variations and distribution in body parts. Our findings showed that these compounds in bee gut vary among colonies, possibly due to the dietary preferences, and are highly concentrated in bodies during the summer. They are distributed differently within bee bodies, with higher concentrations in the abdomens of foragers compared with nurses. Administration of SMCSO in a laboratory setting showed no immediate toxic effects but significantly boosted bees' antioxidant capacity. Long-term administration decreased bee body weight, particularly in the thorax and head, and altered amino acid metabolism. SMCSO is found in the nectar and pollen of rapeseed flowers and highly accumulates in rapeseed honey compared with other types of honey. This study reveals the dual impact of SMCSO on bee health, providing a basis for further ecological and physiological research to enhance bee health and colony sustainability.

Background: Advanced glycation end products (AGEs) are compounds formed by non-enzymatic processes in the Maillard reaction and can cause various chronic diseases. This study explores the AGE formation process in a glucose-amino acid system under both wet- and dry-heating conditions, and analyzes the effect of cysteine in AGE formation., Results: Under wet-heating conditions, N ε -carboxymethyllysine (CML) and N ε -carboxyethyllysine (CEL) concentrations rose for the initial 90 min and subsequently declined after 120 min; after 90 min of heating, the maximum yields in the absence of cysteine were 1151.04 ± 14.01 and 3386.90 ± 26.55 ng mL -1 , respectively. The concentration of pyrraline (Pyr) increased after 30 min and then decreased after 60 min with a maximum yield of 777.68 ± 23.36 ng mL -1 . However, in dry-heating models, the AGE concentrations consistently increased with increasing heating time; the maximum yields for CML, CEL and Pyr were 468.66 ± 10.96, 1993.57 ± 14.81 and 1085.74 ± 58.06 ng mL -1 , respectively. The addition of cysteine showed an inhibitory effect on AGE formation, especially for Pyr in the dry-heating model, with inhibition rates ranging from 17.14% to 95.60%., Conclusion: Although wet-heating models produced more CML and CEL, they produced less Pyr than dry-heating models. The AGE formation in wet-heating models positively correlated with the reaction rate; however, the dry-heating reaction demonstrated a more complex relationship between reaction rate and reaction protocol. Moreover, cysteine exhibited a significant inhibitory effect on AGE production, and the degree of inhibition was proportional to the cysteine concentration. This study provides important insights into the mechanisms for AGE formation under various heating conditions, such as those representing baking (dry-heating) and steaming conditions (wet-heating). © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Objective: Diuretic renal scintigraphy is important in diagnosing pelvi-ureteric junction obstruction (PUJO) in antenatally detected hydronephrotic (ANH) kidneys. Early-phase dynamic renal scintigraphy has several pitfalls contributing to the false interpretation of obstructed drainage, especially after pyeloplasty. This study explores the utility of delayed imaging in 99m Tc-L,L-Ethylenedicysteine (EC) diuretic renal scintigraphy to assess post-pyeloplasty renal drainage in ANH., Methods: Data from May 2019 to January 2024 was retrospectively studied to identify infants with ANH who underwent surgery for PUJO and pre-and post-surgical assessment of renal drainage using 99m Tc-L,L-EC diuretic renal scintigraphy. Dynamic and post-void static images were analyzed to calculate percentage drainage till 3 h. Pre- and post-operative quantitative parameters were compared. Receiver operator curve analysis was done to calculate the threshold drainage to detect renal obstruction on postvoid images., Results: In a cohort of 104 patients with a mean age of 10.1 ± 6.5 months (range 2-36 months) at surgery, 106 renal units (bilateral involvement in two patients) were analyzed. There was no significant difference in the sum of obstructive and equivocal curve patterns (105 vs 79, p = 0.06) and T 1/2 values (105 vs 82, p = 0.093) before and after surgery. However, there was a significant difference between the pre-and post-surgery median 3-h percentage drainage (26 vs 80%, p < 0.001). A drainage threshold of less than 59% at 3 h had 93.4% sensitivity and 92.5% specificity to detect obstructive drainage., Conclusion: Delayed images in diuretic renal scintigraphy are crucial in accurately interpreting post-pyeloplasty drainage patterns and help overcome pitfalls of the dynamic study., Competing Interests: Declarations. Conflict of interest: All authors have no financial disclosures and declare no conflicts of interest. Ethical approval: The Institutional Ethics Committee approved the study (Ref no. IEC-INT/2024/Study-1917). A waiver of individual consent was granted due to the study's retrospective nature., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

A new approach of total major aminothiols determination (cysteine, homocystine, cysteinylglycine, and glutathione) in human plasma by capillary electrophoresis (CE) is presented. It is based on the analytes reduction by tris (2-carboxyethyl) phosphine and derivatization with N-ethylmaleimide, with subsequent ultrafiltration of the sample. Separation was performed using 0.1-M phosphate Na рН 2.48 with 1% Ficoll-400 and 10% methanol. The in-capillary concentration of the analytes was achieved with a pH gradient created via the preinjection of triethanolamine. The absorbance signal was detected at 200 nm. The total analysis time was 16 min (using a silica capillary [50 μm i.d.; total length 42 cm] at a 20-kV voltage). The limits of detection varied from 1.3 μM (glutathione) to 5.4 μM (cysteine). Within-run and between-run precision (CV) was < 7%; reduction of analytes ranging from 91% to 106%, were obtained. The approach was validated on control samples of children's blood plasma. The simplicity of the method and the availability of reagents make the presented approach most suitable for use on standard CE systems., (© 2025 John Wiley & Sons Ltd.)

Objective: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are closely related neurodegenerative conditions within the Lewy body spectrum. The relationship between DLB and PDD remains debated, with ongoing discussion about whether they are distinct diseases or different manifestations of the same disorder. This study aimed to identify differences in cerebral perfusion patterns between DLB and PDD patients., Methods: Single-photon emission computed tomography (SPECT) ethyl cysteinate dimer (ECD) imaging was performed on patients diagnosed with DLB ( n  = 46) and PDD ( n  = 30). The data were acquired by two SPECT/computed tomography systems from two affiliated centers and were retrospectively recruited under the local ethics approval. Relative tracer uptake levels were calculated across 47 automatically determined regions of interest and 240 subregions. A two-sided Welch's t -test was employed to evaluate mean perfusion differences, with results further confirmed through a voxel-wise t -test mapping. The Benjamini-Hochberg procedure was used to adjust P -values for multiple comparisons., Results: The greatest difference in perfusion was in the left associative visual cortex in planes 34 and 36 and the right primary visual cortex in plane 34, with lower mean perfusion observed in PDD patients than those with DLB ( P  = 0.005)., Conclusion: No statistically significant differences in ECD perfusion were found between DLB and PDD patients. The greatest difference was in the visual cortices, where PDD patients suffered a greater loss of perfusion., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The primary objective of the present study is to provide further evidence that the endogenous S-nitrosothiol, S-nitroso-L-cysteine (L-CSNO), plays an essential role in signaling the hypoxic ventilatory response (HVR) in rodents. Key findings were that (1) injection of L-CSNO (50 nmol/kg, IV) caused a pronounced increase in frequency of breathing (Freq), tidal volume (TV) and minute ventilation (MV) in naïve C57BL/6 mice, whereas injection of D-CSNO (50 nmol/kg, IV) elicited minimal responses; (2) L-CSNO elicited minor responses in (a) C57BL/6 mice with bilateral carotid sinus nerve transection (CSNX), (b) C57BL/6 mice treated neonatally with capsaicin (CAP) to eliminate small-diameter C-fibers, and (c) C57BL/6 mice receiving continuous infusion of L-CSNO receptor antagonists, S-methyl-L-cysteine and S-ethyl-L-cysteine (L-SMC + L-SEC, both at 5 μmol/kg/min, IV); and (3) injection of S-nitroso-L-glutathione (L-GSNO, 50 nmol/kg, IV) elicited pronounced ventilatory responses that were not inhibited by L-SMC + L-SEC. Subsequent exposure of naïve C57BL/6 mice to a hypoxic gas challenge (HXC; 10% O 2 , 90% N 2 ) elicited pronounced increases in Freq, TV and MV that were subject to roll-off. These HXC responses were markedly reduced in CSNX, CAP, and L-SMC + L-SEC-infused C57BL/6 mice. Subsequent exposure of all C57BL/6 mice (naïve, CSNX, CAP, and L-SMC + L-SEC) to a hypercapnic gas challenge (5% CO 2 , 21% O 2 , 74% N 2 ) elicited similar robust increases in Freq, TV and MV. Taken together, these findings provide evidence that an endogenous factor with pharmacodynamic properties similar to those of L-CSNO, rather than L-GSNO, mediates the HVR in male C57BL/6 mice., Competing Interests: Declaration of Competing interest The authors declare that this study received funding from Galleon Pharmaceuticals, Inc. and that Santhosh M. Baby was employed by the company Galleon Pharmaceuticals, Inc. The leadership of the company was not directly involved in this study as a commercial entity. Only the principal scientists of the company were involved in the study design, collection, analysis, interpretation of data, the writing of this article, and the decision to submit it for publication. The remaining authors declare that the research described in this manuscript was performed in the complete absence of commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mastitis is an inflammatory disease affecting mammary tissues caused by bacterial infection that negatively affects milk quality and quantity. S-Allylmercaptocysteine (SAMC), a sulfur compound in aged garlic extract (AGE), suppresses lipopolysaccharide (LPS)-induced inflammation in mouse models and cell cultures. However, the mechanisms underlying this anti-inflammatory effect remain unclear. In this study, we demonstrated that oral administration of AGE suppressed the LPS-induced immune response in a mastitis mouse model and that SAMC inhibited LPS-induced interleukin-6 production and nuclear factor κB p65 subunit activation in HC11 mammary epithelial cells. Global phosphoproteomic analysis revealed that SAMC treatment downregulated 910 of the 1,304 phosphorylation sites upregulated by LPS stimulation in mammary cells, including those associated with toll-like receptor 4 (TLR4) signaling. Additionally, SAMC decreased the phosphorylation of 26 proteins involved in pre-mRNA splicing, particularly the U2 small nuclear ribonucleoprotein complex. Furthermore, we found that SAMC increased the production of the myeloid differentiation factor 88 short form (MyD88-S), an alternatively spliced form of MyD88 that negatively regulates TLR4 signaling. These findings suggest that SAMC inhibits TLR4-mediated inflammation via alternative pre-mRNA splicing, thus promoting MyD88-S production in mammary epithelial cells. Therefore, SAMC may alleviate various inflammatory diseases, such as mastitis, by modulating immune responses., Competing Interests: Declarations. Competing interests: M.T., M.K., H.T., and J.I.S. are employed by Wakunaga Pharmaceutical Co., Ltd., and F.Q.Z. is employed by University of Vermont as listed in the affiliation section. The employment does not affect each researcher’s conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript. This study revealed the new biological activity of SAMC in the experiment systems. The company and the University have no financial interest in this publication., (© 2024. The Author(s).)

Cysteine and glutathione can be applied as therapeutic targets in civilization diseases such as diabetes mellitus and cancers. On the other hand, an elevated concentration of homocysteine, and its metabolites such as homocysteine thiolactone and Nɛ-homocysteinyllysine result in health problems and has been indicated as an independent risk factor for cardiovascular disease and accelerated atherosclerosis. This work describes the first simplified HPLC-UV method that allows simultaneous determination of Nɛ-homocysteinyllysine isopeptide, cysteine, glutathione and homocysteine in human plasma. The assay is based on reversed-phase high performance liquid chromatography with UV detection and simultaneous reduction of disulfide bound with tris(2-carboxyethyl)phosphine and the selective pre-column derivatization of the thiol group with 1-benzyl-2-chloropyridinium bromide. Linearities of the detector responses for plasma samples were observed in ranges: 0.1-10.0 nmol/mL for Nɛ-homocysteinyllysine, 2.0-60.0 nmol/mL for glutathione and homocysteine, 20.0-600.0 nmol/mL for cysteine. The proposed method reduces the number of steps, shortens the total time of sample preparation, and limits the amount of single-use polypropylene laboratory materials., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Garlic exhibits hypolipidemic, hypoglycemic, and cardiovascular benefits. The inconsistent results of garlic preparations on adipogenesis have caused more confusion in the public and academia. The compounds responsible for the anti-adipogenesis effect of garlic remain unknown. The present study aimed to verify the real anti-adipogenesis and anti-obesity component in garlic and explored its possible effects in metabolic syndrome. We verified the real anti-adipogenesis and anti-obesity components of garlic in 3T3-L1 preadipocytes and a 10-week-high fat diet (HFD)-induced obese mice. In vitro, two water-soluble and four typical lipid-soluble compounds of garlic were tested for their anti-adipogenesis. Then, the water-soluble compound, alliin, and two processing methods produced garlic oils, were evaluated in vivo study. Mice received oral administration of alliin (25 mg/kg) and garlic oils (15 mg/kg) daily for 8 weeks. Serum lipids, parameters of obesity, and indicators involved in regulating glycolipid metabolism were examined. Our findings confirmed that both water-soluble and lipid-soluble organosulfur compounds of garlic contributed to garlic's anti-adipogenesis effect, in which water-soluble sulfides, especially alliin, exhibited greater potency. Alliin possessed potent effects of anti-obesity and improvement in glucose and lipid metabolism in HFD-induced obese mice. Alliin mediated these effects partly attributed to its modulation of enzymatic activities within glycolipid metabolism and activating PPARγ signaling pathway. In contrast to odorous lipid-soluble sulfides, alliin is odorless, stable, and safe, and is an ideal nutraceutical or even medicinal candidates for the treatment of metabolic diseases. Alliin could be used to standardize the quality of garlic products., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study evaluates the efficacy of SISCOS (Subtraction ictal-interictal SPECT coregistered to SPECT) in localizing the epileptogenic zone (EZ) in focal cortical dysplasia (FCD), comparing its predictive performance with MRI and post-surgical outcomes based on ILAE classification., Methods: 84 patients with drug refractory epilepsy (DRE) who were operated and had histopathology consistent with FCD, were included in the study. All patients had undergone a complete work-up including SISCOS and MRI for EZ localization, followed by discussion in the multidisciplinary epilepsy surgery meeting prior to surgery. Ictal & interictal perfusion SPECT studies were performed with Tc-99 m Ethylene Cysteinate Dimer (Tc-99 m ECD) followed by SISCOS analysis using SPM2 and Bioimage Suite 2.6. Concordance for localization was determined by comparing with the surgical resection site and post-surgical outcomes were assessed using the ILAE classification., Results: The concordance for EZ localization demonstrated by SISCOS was 73.8% and MRI was 82.1%. 52 patients (61.9%) had good surgical outcome and 31(59%) of these were FCD type 2. In patients with discordant MRI findings, SISCOS was able to provide localisation in 86% (13/15), with 69.2% showing good surgical outcomes. Sensitivity of SISCOS and MRI was 73% (95% CI = 59-84.8%) and 78% (95% CI = 67.5-90.3%) respectively with no significant difference between the two. In FCD type I, both SISCOS and MRI revealed a similar a sensitivity of 76.4% (95%CI = 50.1-93.2%). Concordant cases exhibited higher seizure-free odds ratios for both modalities., Conclusion: SISCOS is effective in localizing the EZ in FCD patients, comparable to MRI. Integrating SISCOS and MRI enhances lesion detection, especially in MRI discordant cases. A comprehensive diagnostic approach utilizing SISCOS and MRI can optimize the non-invasive pre-surgical assessment in DRE thereby guiding surgical decision-making in a resource-limited setting., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The present study intended to divulge the potential role of garlic-derived organosulfur compounds (OSCs) in targeting PCSK-9 and averting its interaction with the EGF-A portion of LDL-R via in-vitro and in-silico analysis. Our in-silico screening data showed that 3-(Propylsulfinyl)-L-alanine (PSA), S -Ethyl-L-cysteine (SEC), alliin, and S -Allyl-L-cysteine (SAC) exhibited higher binding energy (-7.05, -7.00, -6.65, and -6.31 Kcal/mol, respectively) against PCSK-9, among other selected OSCs. Further, the protein-protein interaction study of PCSK-9-OSCs-complex with EGF-A demonstrated a similar binding pattern with E-total values ranging from -430.01 to -405.6 Kcal/mol. These results were further validated via in-vitro analysis which showed that SEC, SAC, and diallyl trisulphide (DAT) exhibited the lowest IC 50 values of 4.70, 5.26, and 5.29 µg/mL, respectively. In conclusion, the presented data illustrated that SEC, SAC, and DAT were the best inhibitors of PCSK-9 activity and may have the potential to improve the LDL-R function and lower the circulatory LDL-C level.

Oxidative stress and mitochondrial dysfunction play critical roles in neurodegenerative diseases. Glutathione (GSH), a key brain antioxidant, helps to neutralize reactive oxygen species (ROS) and maintain redox balance. We investigated the effectiveness of L-cysteine (L-Cys) in preventing apoptosis induced by the ROS generator 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) in mouse hippocampal neuronal HT22 cells, as well as alleviating memory and cognitive impairments caused by the GSH synthesis inhibitor L-buthionine sulfoximine (BSO) in mice. DMNQ-induced apoptotic events in HT22 cells, including elevated cytosolic and mitochondrial ROS levels, DNA fragmentation, endoplasmic reticulum stress, and mitochondrial damage-mediated apoptotic pathways were dose-dependently abrogated by L-Cys (0.5-2 mM). The reduced intracellular GSH level, caused by DMNQ treatment, was restored by L-Cys cotreatment. Although L-Cys did not significantly restore GSH in the presence of BSO, it prevented DMNQ-induced ROS elevation, mitochondrial damage, and apoptosis. Furthermore, compared to N-acetylcysteine and GSH, L-Cys had higher 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid radical-scavenging activity. L-Cys also restored mitochondrial respiration capacity in DMNQ-treated HT22 cells by reversing mitochondrial fission-fusion dynamic balance. BSO administration (500 mg/kg/day) in mice led to neuronal deficits, including memory and cognitive impairments, which were effectively mitigated by oral L-Cys (15 or 30 mg/kg/day). L-Cys also reduced BSO-induced ROS levels in the mice hippocampus and cortex. These findings suggest that even though it does not contribute to intracellular GSH synthesis, exogenous L-Cys protects neuronal cells against oxidative stress-induced mitochondrial damage and apoptosis, by acting as a ROS scavenger, which is beneficial in ameliorating neurocognitive deficits caused by oxidative stress., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest relevant to this study., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Sulfur is an essential nutrient for various physiological processes, including protein synthesis and enzyme activation. We aimed to evaluate how S-benzyl-L-cysteine (SBC), an inhibitor of the sulfur assimilation pathway, affects maize plants' growth, photosynthesis, and leaf proteomic profile. Thus, maize plants were grown for 14 days in vermiculite supplemented with SBC. Photosynthesis was assessed using light and CO 2 response curves and chlorophyll a fluorescence. Leaf proteome analysis was conducted to evaluate photosynthetic protein biosynthesis, and ROS content was quantified to assess oxidative stress. Applying SBC resulted in a significant decrease in the growth of maize plants. The gas exchange analysis revealed that maize plants exhibited a diminished rate of CO 2 assimilation attributable to both stomatal and non-stomatal limitations. Furthermore, SBC suppressed the activity of important elements involved in the photosynthetic electron transport chain (including photosystems I and II, cytochrome b 6 f, and ATP synthase) and enzymes responsible for the Calvin cycle, some of which have sulfur-containing prosthetic groups. Consequently, the diminished electron flow rate resulted in a substantial increase in the levels of ROS within the leaves. Our research highlights the crucial role of SBC in disrupting maize photosynthesis by limiting L-cysteine and assimilated sulfur availability, which are essential for the synthesis of protein and prosthetic groups and photosynthetic processes, emphasizing the potential of OAS-TL as a new herbicide site of action., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

To prevent the deterioration of the global environment, the reduction of chemical pesticide use and the development of eco-friendly pest control technologies are urgent issues. Our recent study revealed that the production of reactive oxygen species (ROS) by dual oxidase (Duox) plays a pivotal role in stabilizing the tracheal network by intermediating the tyrosine cross-linking of proteins that constitute trachea. Notably, the formation of dityrosine bonds by ROS can be inhibited by the intake of an antioxidant cysteine derivative N-acetyl-L-cysteine (NAC), which can suppress insect respiration. In this study, we screened for the derivatives showing insecticidal activity and tracheal formation inhibition. As a result of investigating the soybean pest bug Riptortus pedestris, cysteine and methionine derivatives showed respiratory formation inhibition and high insecticidal activity. In particular, NAC had a slow-acting insecticidal effect, while L-cysteine methyl ester (L-CME) showed relatively fast-acting insecticidal activity. Furthermore, the insecticidal activity of these derivatives was also detected in Drosophila, mealworms, cockroaches, termites, and plant bugs. Our results suggest that some antioxidant compounds have specific tracheal inhibitory activity in different insect species and they may be used as novel pest control agents upon further characterization., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Morimura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

SufU, a component of the SufCDSUB Fe-S cluster biosynthetic system, serves as a Zn-dependent sulfur-carrying protein that delivers inorganic sulfur in the form of cysteine persulfide from SufS to SufBCD. To understand this sulfur delivery mechanism, we studied the X-ray crystal structure of SufU and its sulfur-carrying state (persulfurated SufU) and performed functional analysis of the conserved amino acid residues around the Zn sites. Interestingly, sulfur-carrying SufU with Cys41-persulfide (Cys41-S γ -S δ - ) exhibited a unique Zn coordination structure, in which electrophilic S γ is ligated to Zn and nucleophilic/anionic S δ is bound to distally conserved Arg125. This structure is distinct from those of other Cys-persulfide-S δ -ligated metals of metalloproteins, such as hybrid cluster proteins and SoxAX. Functional analysis of SufU variants with Zn-ligand and Arg125 substitutions revealed that both Zn and Arg125 are critical for the function of SufU with SufS. The Zn-persulfide structure of SufU provides insight into the sulfur-transfer process, suggesting that persulfide-S δ - is stabilized via bridging by Zn and Arg125 of SufU.

Cardiomyocyte injury is closely related to various myocardial diseases, and S-Allyl-L-cysteine (SAC) has been found to have myocardial protective effects, but its mechanism is currently unclear. Meanwhile, copper also has various physiological functions, and this study found that copper inhibited cell viability in a concentration and time-dependent manner, and was associated with multiple modes of death. Elesclomol plus CuCl 2 (ES + Cu) significantly inhibited cell viability, and this effect could only be blocked by copper chelator TTM, indicating that "ES + Cu" induced cuproptosis in cardiomyocytes. SAC reduced the inhibitory effects of high concentration copper and "ES + Cu" on cell viability in a concentration and time-dependent manner, indicating that SAC plays a cardioprotective role under stress. Further mechanism study showed that high concentration of copper significantly induced cardiomyocyte apoptosis and increased the levels of LDH, MDA and ROS, while SAC inhibited the apoptosis and injury of cardiomyocytes induced by copper. "ES + Cu" significantly increased intracellular copper levels and decreased the expression of FDX1, LIAS, Lip-DLST and Lip-DLAT; FDX1 siRNA did not affect the expression of LIAS, but further reduced the expression of Lip-DLST and Lip-DLAT; SAC did not affect the expression of these genes, but enhanced the effect of "ES + Cu" in down-regulating these gene expression and restored intracellular copper levels. In addition, "ES + Cu" reduced ATP production, weakened the activity of mitochondrial complex I and III, inhibited cell viability, and increased the contents of injury markers LDH, MDA, CK-MB and cTnI, while SAC significantly improved mitochondrial function injury and cardiomyocyte injury induced by "ES + Cu". Therefore, SAC can inhibit apoptosis and cuproptosis to play a cardioprotective role., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The Cingulate Island score (CIScore) is useful index for differentiating between dementia with Lewy body (DLB) and Alzheimer's disease (AD) using regional cerebral blood flow (rCBF) SPECT. The Z score standing for medial temporal lobe (MTL) atrophy and the ratio of Z score between dorsal brain stem (DBS) to MTL are useful indices for differentiating between DLB and AD using MRI with VSRAD. The current study investigated the diagnostic ability by the combined use of rCBF SPECT and MRI in the differentiation between AD and DLB., Materials and Methods: In cases with 42 AD and 28 DLB undertaken Tc-99m-ECD SPECT and MRI, we analyzed differential diagnostic ability between AD and DLB among following conditions by single or combined settings. Namely, they were (1) the CIScore as a parameter of rCBF SPECT (DLB ≦ 0.25), (2) Z score value of MTL atrophy (DLB ≦ 2.05), (3) the ratio of Z score of DBS to medial temporal gray matter as a parameter of brain atrophy using VSRAD (DLB ≧ 0.38). Also, we analyzed them both including and omitting the elderly (over 75 years old)., Results: The accuracy of differential diagnosis in this condition was 74% for (1), 69% for (2), and 67% for (3). The accuracy by combination condition was 84% for (1) and (2), 81% for (1) and (3), and 67% for (2) and (3), respectively. The combination method by CIScore and the Z score of MTL showed the best accuracy. When we confined condition to ages younger than 75 years, the accuracy improved to 94% in the combination method., Conclusion: The combined use of CIScore and Z score of MTL was suggested to be useful in the differential diagnosis between DLB and AD particularly in younger than 75 years old., (© 2024. The Author(s).)

Background and Aims: Acetaminophen (APAP) hepatotoxicity and ischemic hepatic injury (IH) demonstrate remarkably similar biochemical patterns. Deciding between these two etiologies in the setting of acute liver failure (ALF) can be challenging. We reviewed all cases in the Acute Liver Failure Study Group (ALFSG) registry where these diagnoses were considered, to determine reasons for, and frequency of, difficulties making these diagnoses. We hypothesized that the newly developed APAP-CYS adduct assay could help in discerning the correct diagnosis., Methods: Among 3364 patients with ALF or acute liver injury (ALI: INR ≥ 2.0 but without encephalopathy) between 1998 and 2019, 1952 (58%) received a final diagnosis of either APAP (1681) or IH (271). We utilized a review committee of senior hepatologists as well as the APAP-CYS assay (where sera were available), measuring the presence of toxic by-products of APAP injury to optimize adjudication., Results: With these methods, a total of 575 adduct positive APAP cases included 488 recognized APAP, as well as an additional 87 patients previously diagnosed as other etiologies. Nine cases initially attributed to IH were deemed combination APAP-IH injuries. Conversely, 215 of the 280 IH subjects tested for adducts disclosed 173 confirmed as IH with adduct testing below the toxicity threshold, while 9 cases were revised from APAP to the IH-APAP combination phenotype, where both hypotension and APAP likely played a role., Conclusions: Discerning APAP from IH can be difficult-in rare cases, combined injury is observed (18/1952). APAP-CYS testing resulted in revising the diagnosis in 14.6% of cases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

1,3-Butadiene (BD) is a carcinogenic air pollutant. N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (MHBMA3 or 4HBeMA), an urinary BD metabolite with unspecified configuration, is considered the most sensitive BD biomarker and has been used in routine biomonitoring since 2012. However, two issues remain unaddressed: why its concentrations are unusually high relative to other urinary BD biomarkers and why some authors reported no detection of the biomarker whereas other authors readily quantitated it. To address the issues, we synthesized and structurally characterized the authentic trans- and cis-isomers of MHBMA3 (designated NE and NZ, respectively), developed an isotope-dilution LC-MS/MS method for their quantification, and examined 67 urine samples from barbecue restaurant personnel (n = 47) and hotel administrative staff (n = 20). The restaurant personnel were exposed to barbecue fumes, which contain relatively high concentrations of BD. The results showed that NE and NZ had highly similar NMR spectra, and were difficult to be well separated chromatographically. The NMR data showed that the MHBMA3 isomer investigated in most previous studies was NE. We did not detect NE and NZ in any samples; however, an interfering peak with varying heights was observed in most samples. Notably, under the chromatographic conditions used in the literature, the peak exhibited indistinguishable retention time from that of NE. Thus, it is highly likely that the interfering peak has been mis-identified as NE in previous studies, providing a reasonable explanation for the high MHBMA3 concentration in urine. The contradiction in the presence of MHBMA3 in urine was also caused by the mis-identification, because the researchers who reported the absence of MHBMA3 were actually detecting NZ. Thus, we clarified the confusion on MHBMA3 in previous studies through correctly identifying the two MHBMA3 isomers. The presence of NE and NZ in human urine warrants further investigations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Endometriosis is a female hormone-dependent gynecological disorder characterized by chronic inflammation. Therefore, the development of novel treatment strategies that can diminish the side effects of the long-term use of hormone-based drugs has been emphasized. S-Allyl-L-cysteine (SAC) is the major constituent of aged garlic extracts. Although the therapeutic effects resulting from the antioxidant properties of SAC have been extensively studied in inflammatory diseases, the therapeutic efficacy of SAC in endometriosis has not been described. In this study, we investigated the therapeutic potential of SAC for endometriosis using a mouse model., Methods: An endometriosis mouse model was surgically induced, and oral treatment with 30 mg/kg SAC was administered daily for 28 days. The development of endometriotic lesions was assessed by histological analysis, and the expression profiles of adhesion-, apoptosis-, and inflammation-related genes were evaluated by PCR. Flow cytometric analysis of mouse spleen was conducted to assess changes in lymphocyte subpopulations., Results: SAC treatment significantly inhibited endometriotic lesion growth. Transcriptional expression analysis revealed the antiadhesion and apoptosis-promoting effects of SAC. In particular, SAC showed an effective immune modulatory response by altering splenic CD4 + and CD8 + T cell subsets and inflammatory cytokine production in the spleen and endometriotic lesions., Conclusion: This study newly elucidates the inhibitory effects of SAC on the growth of endometriosis in a mouse model and describes its immunomodulatory effects., (© 2024. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

Atrial fibrillation (AF) is the most prevalent sustained tachyarrhythmia in patients with cardiovascular diseases. Recently, it has been discovered that oxidative stress is an important contributor to AF. Therefore, antioxidant therapies for AF have great potential for clinical applications. Methionine, a sulfur-containing amino acid residue other than cysteine, is recognized as a functional redox switch, which could be rescued from the reversible oxidation of methionine sulfoxide by methionine sulfoxide reductase A (MsrA). S -Methyl-L-cysteine (SMLC), a natural analogue of Met, which is abundantly found in garlic and cabbage, could substitute for Met oxidations and mediate MsrA to scavenge free radicals. However, whether SMLC alleviates AF is unclear. This study aims to clarify the effects of SMLC on AF and elucidate the underlying pharmacological and molecular mechanisms. In vivo , SMLC (70, 140 and 280 mg kg -1 day -1 ) was orally administered to mice for 4 weeks with angiotensin II (Ang II) by subcutaneous infusion using osmotic pumps to induce AF. Ang II significantly prompted high AF susceptibility and atrial remodeling characterized by oxidative stress, conductive dysfunction and fibrosis. SMLC played a remarkable protective role in Ang II-induced atrial remodeling dose-dependently. Moreover, RNA sequencing was performed on atrial tissues to identify the differentially expressed mRNA, which was to screen out MSRA, CAMK2 and MAPK signaling pathways. Western blots confirmed that Ang II-induced downregulation of MsrA and upregulation of oxidized CaMKII (ox-CaMKII) and p38 MAPK could be reversed in a concentration-dependent manner by SMLC. To investigate the underlying mechanisms, HL-1 cells (mouse atria-derived cardiomyocytes) treated with Ang II were used for an in vitro model. SMLC alleviated Ang II-induced cytotoxicity, mitochondrial damage and oxidative stress. Additionally, knockdown MsrA could attenuate the protective effects of SMLC, which were eliminated by the p38 MAPK inhibitor SB203580. In summary, the present study demonstrates that SMLC protects against atrial remodeling in AF by inhibiting oxidative stress through the mediation of the MsrA/p38 MAPK signaling pathway.

Sulforaphene (4-methylsufinyl-3-butenyl isothiocyanate, SFE), produced by myrosinase hydrolysis of glucoraphenin (4-methylsulfinyl-3-butenyl glucosinolate) found in radish seeds, is strongly associated with cancer prevention. In this study, we investigated the stability of SFE (purity above 98%) under various thiol-containing compounds at 25 °C, such as sodium hydrosulfide (NaHS), glutathione (GSH), and cysteine (Cys). We observed that the degradation of SFE was closely related to the presence and dissociation capacity of thiol-containing compounds in the solution, particularly the thiol group. We found that the degradation rate of SFE was influenced by incubation with NaHS, GSH, and Cys, with distinct degradation products detected for each of these thiol-containing compounds. Compared to GSH, sulfide and Cys played important roles in promoting the degradation of SFE. Furthermore, we found substantial quantities of hydrogen sulfide in conjunction with SFE during the hydrolysis process of seeds, and a heat treatment of the seeds resulted in increased production of SFE. However, the introduction of sulfide-oxidizing bacteria to the hydrolytic system did not exhibit any inhibitory effect on the degradation of SFE. These results provided a guideline for industries to improve the stability of SFE during preparation.

Background: Endurance is an important capacity to sustain healthy lifestyles. Aged garlic extract (AGE) has been reported to exert an endurance-enhancing effect in clinical and animal studies, although little is known about its active ingredients and mechanism of action., Objectives: This study investigated the potential effect of S-1-propenylcysteine (S1PC), a characteristic sulfur amino acid in AGE, on the swimming endurance of mice, and examined its mechanism of action by a metabolomics-based approach., Methods: Male Institute of Cancer Research (ICR) mice (6 wk old) were orally administered either water (control) or S1PC (6.5 mg/kg/d) for 2 wk. The swimming duration to exhaustion was measured at 24 h after the final administration. Nontargeted metabolomic analysis was conducted on the plasma samples obtained from mice after 40-min submaximal swimming bouts. Subsequently, the enzyme activity of carnitine acyltransferase-1 (CPT-1) and the content of malonyl-coenzyme A (CoA), acetyl-CoA, and adenosine triphosphate (ATP) were quantified in heart, skeletal muscles, and liver of mice., Results: The duration time of swimming was substantially increased in the S1PC-treated mice as compared with the control group. Metabolomic analysis revealed significant alterations in the plasma concentration of the metabolites involved in fatty acid metabolism, in particular medium- or long-chain acylcarnitines in the mice treated with S1PC. Moreover, the administration of S1PC significantly enhanced the CPT-1 activity with the concomitant decrease in the malonyl-CoA content in the heart and skeletal muscles. These effects of S1PC were accompanied by the elevation of the acetyl-CoA and ATP levels to enhance the energy production in those tissues., Conclusions: S1PC is a key constituent responsible for the endurance-enhancing effect of AGE. This study suggests that S1PC helps provide energy during endurance exercise by increasing fatty acid metabolism via CPT-1 activation in the heart and skeletal muscles., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: High moisture meat analog (HMMA) products processed using extrusion have become increasingly popular in the last few years. Because the formation of disulfide bonds is believed to play a critical role in the texturization mechanism, this study aimed to understand how chemical compounds capable of reducing disulfide bonds, specifically cysteine, sodium metabisulfite, and glutathione, affect the texture and the chemical interactions between the proteins., Method: Wheat protein blended with cysteine, sodium metabisulfite, or glutathione at levels of 0, 0.5, 1.0, 2.5, 5.0, and 7.5 g kg -1 was extruded at three different temperatures (115, 140, and 165 °C) using a co-rotating twin-screw extruder. The feed rate (85 g min -1 ), the moisture content (600 g kg -1 ), and the screw speed (300 rpm) were kept constant. Unextruded and extruded material was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, polymeric protein fractionation, and sulfhydryl group/disulfide bond analysis. Extruded samples were further analyzed for their hardness and their anisotropic index., Results: The inclusion of reductants significantly affected the structure of the obtained extrudates. Although reducing agents had a relatively small impact on the total amount of disulfide bonds, their action significantly enhanced crosslinking between the proteins. At select conditions, samples with high fibrousness were specifically obtained when cysteine or sodium metabisulfite was included at levels of 5.0 g kg -1 ., Discussion: In the presence of reducing agents, it is believed that disulfide bonds are split earlier during the process without binding to them, giving the protein strands more time to unravel and align, leading to a better flow behavior and more fibrous products. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Hot compressed water (HCW), also known as subcritical water (SCW), refers to high-temperature compressed water in a special physical and chemical state. It is an emerging technology for natural product extraction. The volatile organic compounds (VOCs) generated from the Maillard reaction between l-ascorbic acid (ASA) and l-cysteine (Cys) have attracted significant interest in the flavor and fragrance industry. This study aimed to explore the formation mechanism of VOCs from ASA and Cys and examine the effects of reaction parameters such as temperature, time, and pH in HCW., Results: The identified VOCs were predominantly thiophene derivatives, polysulfides, and pyrazine derivatives in HCW. The findings indicated that thiophene derivatives were formed under various pH conditions, with polysulfide formation favored under acidic conditions and pyrazine derivative formation preferred under weak alkaline conditions, specifically at pH 8.0., Conclusion: The Maillard reaction between ASA and Cys mainly produced thiophene derivatives, polysulfides, and pyrazine derivatives in HCW. The generation mechanism was significantly dependent on the surrounding pH conditions. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Introduction: It is important to distinguish Waldenström macroglobulinemia from smoldering Waldenström macroglobulinemia (sWM), because only patients with Waldenström macroglobulinemia require treatment, however the distinction can be clinically complex. The aim of this study is to investigate whether [ 68 Ga]Ga-pentixafor PET/CT shows different characteristics in sWM and Waldenström macroglobulinemia patients and therefore can help to differentiate Waldenström macroglobulinemia and sWM., Results: Thirty-seven patients with newly diagnosed Waldenström macroglobulinemia and 11 sWM patients were analyzed [35 men and 13 women; 64.3 ± 10.7 (range, 29-87) years old]. The SUV max of bone marrow disease, lymph nodes, and other extramedullary diseases on [ 68 Ga]Ga-pentixafor were significantly higher than those on 2-[ 18 F]FDG PET/CT ( P  < 0.05). On [ 68 Ga]Ga-pentixafor PET/CT, patients with Waldenström macroglobulinemia had more lymph node regions involved, significantly higher incidence of involvement in more than three lymph node regions, larger nodal disease, and higher incidence of other extramedullary disease when compared with sWM patients ( P  < 0.05). Waldenström macroglobulinemia patients showed significantly higher total lesions uptake, total lesion volume, and SUV max of extramedullary disease than sWM patients did ( P  < 0.05). None of the visual or semiquantitative indexes in 2-[ 18 F]FDG PET/CT showed significant difference between Waldenström macroglobulinemia and sWM patients., Conclusion: [ 68 Ga]Ga-pentixafor PET/CT had better diagnostic performance than 2-[ 18 F]FDG PET/CT in Waldenström macroglobulinemia. Patients with Waldenström macroglobulinemia presented with more extensive extramedullary disease shown in [ 68 Ga]Ga-pentixafor PET/CT than sWM patients did., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Cysteine thiols are susceptible to various oxidative posttranslational modifications (PTMs) due to their high chemical reactivity. Thiol-based PTMs play a crucial role in regulating protein functions and are key contributors to cellular redox signaling. Although reversible thiol-based PTMs, such as disulfide bond formation, S-nitrosylation, and S-glutathionylation, have been extensively studied for their roles in redox regulation, thiol sulfinic acid (-SO 2 H) modification is often perceived as irreversible and of marginal significance in redox signaling. Here, we revisit this narrow perspective and shed light on the redox regulatory roles of -SO 2 H in plant stress signaling. We provide an overview of protein sulfinylation in plants, delving into the roles of hydrogen peroxide-mediated and plant cysteine oxidase-catalyzed formation of -SO 2 H, highlighting the involvement of -SO 2 H in specific regulatory signaling pathways. Additionally, we compile the existing knowledge of the -SO 2 H reducing enzyme, sulfiredoxin, offering insights into its molecular mechanisms and biological relevance. We further summarize current proteomic techniques for detecting -SO 2 H and furnish a list of experimentally validated cysteine -SO 2 H sites across various species, discussing their functional consequences. This review aims to spark new insights and discussions that lead to further investigations into the functional significance of protein -SO 2 H-based redox signaling in plants., (© 2024 John Wiley & Sons Ltd.)

Growing evidence indicates that the intake of trans fatty acids (TFAs) increases the risk of numerous diseases, such as cardiovascular diseases. Recently, our group found that certain natural sulfur compounds (allyl isothiocyanate [AITC] and diallyl disulfide [DADS]) promote cis to trans isomerization of fatty acid esters during heat treatment. However, little information is available on the fatty acid isomerization with them. In this study, we investigated the effects of oxygen and α-tocopherol (antioxidant) on isomerization of oleic acid (18:1) methyl ester (OA-ME) in the presence of AITC and DADS. Furthermore, the effect of the simultaneous use of AITC and DADS was evaluated. Our results indicate that oxygen enhances the AITC-induced trans isomerization, and DADS was found to promote trans isomerization but inhibit AITC-induced trans isomerization during heating. Both AITC- and DADS-induced trans isomerization were inhibited by α-tocopherol. These results indicate that the trans isomerization of fatty acids induced by sulfur compounds can be controlled by devising a cooking process and the food ingredients used together.

Garlic is a vegetable with numerous pro-health properties, showing high antioxidant capacity, and cytotoxicity for various malignant cells. The inhibition of cell proliferation by garlic is mainly attributed to the organosulfur compounds (OSCs), but it is far from obvious which constituents of garlic indeed participate in the antioxidant and cytotoxic action of garlic extracts. This study aimed to obtain insight into this question by examining the antioxidant activity and cytotoxicity of six OSCs and five phenolics present in garlic. Three common assays of antioxidant activity were employed (ABTS ● decolorization, DPPH ● decolorization, and FRAP). Cytotoxicity of both classes of compounds to PEO1 and SKOV-3 ovarian cancer cells, and MRC-5 fibroblasts was compared. Negligible antioxidant activities of the studied OSCs (alliin, allicin, S -allyl-D-cysteine, allyl sulfide, diallyl disulfide, and diallyl trisulfide) were observed, excluding the possibility of any significant contribution of these compounds to the total antioxidant capacity (TAC) of garlic extracts estimated by the commonly used reductive assays. Comparable cytotoxic activities of OSCs and phenolics (caffeic, p -coumaric, ferulic, gallic acids, and quercetin) indicate that both classes of compounds may contribute to the cytotoxic action of garlic.

Renal cell carcinoma (RCC) accounts for 2% of all cancer cases worldwide, and majority are sporadic. The latest World Health Organization (WHO) classification of renal cell tumors (fifth edition, 2022) has molecularly defined renal tumor entities, which includes fumarate hydratase (FH)-deficient RCC. FH-deficient RCC is an aggressive carcinoma caused by pathogenic alterations in FH gene, seen in 15% of patients with hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) syndrome. These tumors occur more frequently at a younger age and present at an advanced stage, carrying a dismal prognosis. We report a series of 10 cases of FH-deficient RCC. The mean age was 49.8 years, and all cases presented in advanced stages (III and IV). Morphologically, the cases had varied architectural patterns with characteristic eosinophilic macronucleoli and perinucleolar halo. On immunohistochemistry (IHC), all showed diffuse nucleo-cytoplasmic expression of S-(2-succino)-cysteine (2-SC), with loss of FH in seven cases. FH-deficient RCCs are aggressive neoplasms and can be diagnosed using specific IHC markers (FH and 2-SC). These patients should undergo germline testing for FH gene mutation, genetic counseling, and surveillance of family members., (© 2024 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Background: Cerebral infarction, formerly known as ischemic stroke, refers to localized ischemic necrosis or softening caused by disorders of blood supply to the brain, ischemia, or hypoxia. Cerebral infarction is characterized by high mortality and morbidity. Therefore, early and accurate diagnosis of cerebral infarction is of great significance to the selection of treatment and prognosis of patients. Electrocardiogram (ECG) is the traditional method for diagnosing myocardial infarction. However, ECG diagnosis of myocardial infarction based on electrophysiological manifestations of cardiac electrostimulation can only indirectly reflect the anatomical lesions, and can not diagnose the lesions in special parts of the heart, so there are diagnostic limitations, there will be certain missed diagnosis and misdiagnosis., Objective: Our study aimed to assess the effect of carotid Doppler ultrasound combined with cysteine, D dimer, and other indexes in the clinical diagnosis of cerebral infarction, in order to provide effective basis for early diagnosis and treatment of cerebral infarction patients., Design: This study was a retrospective study., Setting: This study was carried out in First Affiliated Hospital, Anhui University of Science and Technology (Huainan First People's Hospital) from November 2020 to December 2022., Participants: A total of 40 patients with cerebral infarction were selected as the observation group (OG). At the same time, 40 healthy people who underwent physical examinations were selected as the control group (CG). There were 21 males and 19 females in the OG. The age ranged from 59 to 76 years, with an average of (67.11±0.23) years. There were 23 males and 17 females in the CG. The age ranged from 58 to 77 years, with an average of (68.04±0.35) years., Interventions: Both groups of subjects underwent carotid Doppler ultrasound examination to observe the number of carotid plaque formation, the carotid artery intimal thickness and the lumen diameter. Besides, serum homocysteine (Hcy) and cystatin C (Cys-C) levels of the subjects were detected by an automatic biochemical analyzer and supporting reagents. The serum high sensitivity C reactive protein (hsCRP) levels of the two groups were detected by immune turbidimetry. The plasma levels of D-dimer (D-D) and fibrinogen (FIB) were detected by immunoturbidimetric method. Receiver operating characteristic (ROC) curve was implemented to analyze the value of Color Carotid Doppler ultrasound combined with Hcy, Cys-C, hsCRP, D-D and FIB detection in diagnosing cerebral infarction., Outcome Measures: (1) Carotid Doppler ultrasound can observe cardiac morphological changes from multiple angles and planes, and diagnose myocardial infarction according to the changes of ventricular wall structure caused by myocardial ischemia. It has the advantages of simple operation and high image quality. (2) The hemodynamic parameters of the bilateral common carotid artery and internal carotid artery, (3) Serum Hcy, Cys-C, and hsCRP levels, as well as plasma levels of D-D and FIB. Hcy is an independent risk factor for cardiovascular and cerebrovascular diseases, and the Hcy level is directly related to the pre-onset of cerebral infarction patients. Cys-C is an ideal endogenous marker to reflect the change of glomerular filtration rate. In recent years, it has been found that the interaction of Cys-C, Hcy and cathepsin is involved in the pathological process of cardiovascular diseases such as atherosclerosis, aneurysm and myocardial infarction. hsCRP can reflect left ventricular function, myocardial injury, inflammation and other conditions, which is helpful to evaluate the condition of cerebral infarction patients. D-D can reflect the coagulation function of the body, and its high expression can indicate that the body is in a state of hypercoagulation, accompanied by secondary hyperfibrinolysis, and is often used in the clinical diagnosis of cerebral infarction. FIB is an important factor contributing to atherosclerosis and plays an important role in the occurrence and development of cerebral infarction. (4) ROC curve results., Results: The number of carotid plaque formation in the OG was significantly higher compared to the CG (P < .05). The carotid artery intimal thickness in the OG was relatively elevated relative to the CG (P < .05). The lumen diameter was smaller in the OG compared to the CG (P < .05). The peak systolic velocity and end-diastolic velocity of the left and right common carotid artery and the left and right internal carotid artery in the OG declined compared to the CG, and the resistance index of the left and right common carotid artery and the left and right internal carotid artery in the OG was elevated compared to the CG (P < .05). The serum levels of Hcy, Cys-C, and hsCRP, as well as plasma levels of D-D and FIB in the OG, were elevated compared to the CG (<.05). The sensitivity and specificity of Color Carotid Doppler ultrasound combined with Hcy, Cys-C, hsCRP, D-D and FIB in the diagnosis of AMI were 0.919 and 0.817 respectively, significantly higher than that predicted by alone (P < .001)., Conclusions: Carotid Doppler ultrasound combined with cysteine, D dimer, and other indexes played an important role in the clinical diagnosis of cerebral infarction, which was worthy of promotion. Our experimental results provide an important basis for the clinical scientific application of Carotid Doppler ultrasound and myocardial marker detection, especially for those AMI patients with no abnormal changes in ECG and no obvious clinical symptoms, it can realize early diagnosis and timely treatment, and reduce the mortality of AMI.

Limited alliinase resources cause difficulties in the biosynthesis of thiosulfinates (e.g., allicin), restricting their applications in the agricultural and food industries. To effectively biosynthesize thiosulfinates, this study aimed to excavate bacterial alliinase resources and elucidate their catalytic properties. Two bacterial cystathionine β-lyases (MetCs) possessing high alliinase activity (>60 U mg -1 ) toward L-(-)-alliin were identified from Allium sativum rhizosphere isolates. Metagenomic exploration revealed that cystathionine β-lyase from Bacillus cereus (BcPatB) possessed high activity toward both L-(±)-alliin and L-(+)-alliin (208.6 and 225.1 U mg -1 ), respectively. Although these enzymes all preferred l-cysteine S-conjugate sulfoxides as substrates, BcPatB had a closer phylogenetic relationship with Allium alliinases and shared several similar features with A. sativum alliinase. Interestingly, the Trp 30 Ile 31 Ala 32 Asp 33 Met 34 motif in a cuspate loop of BcPatB, especially sites 31 and 32 at the top of the motif, was modeled to locate near the sulfoxide of L-(+)-alliin and is important for substrate stereospecificity. Moreover, the stereoselectivity and activity of mutants I31V and A32G were higher toward L-(+)-alliin than those of mutant I31L/D33E toward L-(-)-alliin. Using bacterial alliinases and chemically synthesized substrates, we obtained thiosulfinates with high antimicrobial and antinematode activities that could provide insights into the protection of crops and food.

Objectives: Conventional hair permanent waving (PW) and permanent straightening processes typically involve two steps: reduction, for breaking -S-S- bond in cystine into cysteine and oxidation for -S-S- bond reconnection. However, it is known that the hair incurs damage during the oxidation step. In this work, we proposed a novel strategy to reconnect reduced disulfide bonds in hair via the thiol-Michael click reaction, by using a symmetric Michael reagent., Methods: Virgin black Chinese hair was reduced using 8% wt thioglycolic acid and employed as model hair containing a high content of broken disulfide bonds. The reduced hair was treated with 1,4-n-butylene dimaleate. Raman spectroscopy and Fourier transform infrared spectroscopy (FT-IR) were used to verify the chemical changes occurred in untreated and treated hair fibre. Single-fibre mechanical properties and thermal properties of the hair were evaluated using tensile testing and differential scanning calorimetry (DSC), respectively., Results: The 1,4-n-butylene dimaleate could reconnect free thiol groups generated by disulfide bond reduction via thiol-Michael click reaction and significantly improve the mechanical strength of hair compared to that of the reduced hair. Secondary conformational resolution analysis of FT-IR results revealed that the content of α-helix structure could be restored after treatment with 1,4-n-butylene dimaleate. The intermolecular forces established by the newly generated C-S bonds compensate the broken disulfide bonds and enhance the fracture strength of the hair compared to that of reduced hair. Michael reagents of similar structure also showed similar performance in restoring the mechanical properties of reduced hair., Conclusions: Our data suggest that 1,4-n-butylene dimaleate can restore the mechanical properties of reduced hair by reconnecting reduced disulfide bonds and restoring the secondary conformation of hair keratin., (© 2024 Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Staphylococcus aureus is a major human pathogen that can cause infections that range from superficial skin and mucosal infections to life threatening disseminated infections. S. aureus can attach to medical devices and host tissues and form biofilms that allow the bacteria to evade the host immune system and provide protection from antimicrobial agents. To counter host-generated oxidative and nitrosative stress mechanisms that are part of the normal host responses to invading pathogens, S. aureus utilizes low molecular weight (LMW) thiols, such as bacillithiol (BSH). Additionally, S. aureus synthesizes its own nitric oxide (NO), which combined with its downstream metabolites may also protect the bacteria against specific host responses. We have previously shown that LMW thiols are required for biofilm formation in Mycobacterium smegmatis and Pseudomonas aeruginosa. Here, we show that the S. aureus bshC mutant strain, which is defective in the last step of the BSH pathway and lacks BSH, is impaired in biofilm formation. We also identify a possible S-nitrosobacillithiol reductase (BSNOR), similar in sequence to an S-nitrosomycothiol reductase found in M. smegmatis and show that the putative S. aureus bsnoR mutant strain has reduced levels of BSH and decreased biofilm formation. Our studies also show that NO plays an important role in biofilm formation and that acidified sodium nitrite severely reduces biofilm thickness. These studies provide insight into the roles of oxidative and nitrosative stress mechanisms on biofilm formation and indicate that BSH and NO are key players in normal biofilm formation in S. aureus., Competing Interests: Declaration of competing interest Clarissa J. Nobile is an associate editor for Microbial Pathogenesis. Clarissa J. Nobile is a cofounder of BioSynesis, Inc., a company developing diagnostics and therapeutics for biofilm infections. Megha Gulati was a consultant for BioSynesis, Inc. The confocal scanning laser microscopy images in this work were taken using a confocal microscope acquired through the National Science Foundation (NSF) MRI award DMR-1625733. This work was supported by the National Institutes of Health (NIH) National Institute of General Medical Sciences (NIGMS) award R35GM124594 to CJN, by the NIH NIGMS award SC3GM100855 and National Science Foundation (NSF) award MCB1244611 to MR, and by the NIH National Institutes of Allergy and Infectious Diseases (NIAID) award R15AI137975 to ADH. CLE was supported by fellowship F31DE028488 from the NIH National Institute of Dental and Craniofacial Research (NIDCR). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: High glucose (HG)-induced oxidative stress is associated with apoptosis in pancreatic β-cells. The protective effect of astaxanthin-s-allyl cysteine diester (AST-SAC) against HG-induced oxidative stress in pancreatic β-cells (βTC-tet cell line) in in vitro was studied. Materials and Methods: βTC-tet cell line was exposed to HG in the presence and absence of AST-SAC. Various parameters such as cell viability, reactive oxygen species generation, mitochondrial membrane potential, DNA fragmentation and expression of proteins involved in apoptosis [p53, B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax), cytochrome c and caspase 3] were studied. Results: Pre-treatment of βTC-tet cells with AST-SAC (4, 8 and 12 μg/ml) in the presence of HG (25 mM) protected the viability of the cells in a dose-dependent manner. AST-SAC treatment mitigated the oxidative stress thereby preventing the mitochondrial dysfunction, DNA damage and apoptosis in βTC-tet cells against HG toxicity. Treatment with AST-SAC prevented the increased expression of p53 under HG conditions. Further, AST-SAC treatment maintained the level of pro-apoptotic (Bax, cleaved caspase-3 and cytochrome c) and anti-apoptotic (Bcl-2) proteins to that of the control level under HG exposed conditions in βTC-tet cells. Conclusion: Altogether, AST-SAC alleviated HG-induced oxidative damage and apoptosis in pancreatic β-cells by enhancing the antioxidant status and altering apoptotic-related protein expression.

Purpose: The aim of this study was to develop a novel approach that enhanced diagnostic accuracy in the diagnosis of mild cognitive impairment (MCI) and early Alzheimer's disease (AD) using cerebral perfusion SPECT by minimizing artifacts caused by cerebral atrophy., Materials and Methods: [ 99m Tc]-ECD and SPECT studies were performed on 15 cognitively normal patients, 40 patients with MCI, and 16 patients with AD. SPECT images were compared using SPM. The atrophy correction method was incorporated to reduce artifacts through the MRI masking procedure. Regional Z-score, percent extent, and atrophy correction rate were obtained and compared. The Z-score mapping program was structured as a single package that ran semi-automatically., Results: The method significantly reduced regional Z-score in most regions, leading to improved estimates. The mean atrophy correction rate ranged from 10.4 to 12.0%. In MCI and AD, the convexities of the frontal and parietal lobes and the posterior medial cerebrum were particularly sensitive to cerebral atrophy, and the Z-scores were overestimated, whereas the posterior cingulate cortex and the cerebellum were less sensitive. The diagnostic accuracy for MCI increased from 67 to 69% and for AD from 78 to 82%., Conclusion: The proposed approach provided more precise Z-scores with less over- or underestimation, artifacts, and improved diagnostic accuracy, being recommended for clinical studies., (© 2024. The Author(s).)

The extensive utilization of mulch films in agricultural settings, coupled with the persistence of microplastic remnants in soil following the natural degradation of plastics, has given rise to detrimental microplastic impacts on crops. Arsenic (As) contamination in the environment is known to accumulate in crops through aquatic pathways or soil. Garlic (Allium sativum L.), a globally popular crop and seasoning, contains alliin, a precursor of its flavor compounds with medicinal properties. While alliin exhibits antimicrobial and antioxidant effects in garlic, its response to microplastics and arsenic has not been thoroughly investigated, specifically in terms of microplastic or As uptake. This study aimed to explore the impact of varied stress concentrations of microplastics on the toxicity, migration, and accumulation of As compounds. Results demonstrated that polystyrene (PS) fluorescent microspheres, with an 80 nm diameter, could permeate garlic bulbs through the root system, accumulating within vascular tissues and intercellular layers. Low concentrations of PS (10 and 20 mg L -1 ) and As (2 mg L -1 ) mitigated the production and accumulation of reactive oxygen species (ROS) and antioxidant enzymes in garlic. Conversely, garlic exhibited reduced root vigor, substance uptake, and translocation when treated with elevated As concentrations (4 mg L -1 ) in conjunction with PS concentrations of 40 and 80 mg L -1 . An escalation in PS concentration facilitated As transport into bulbs but led to diminished As accumulation and biomass in the root system. Notably, heightened stress levels weakened garlic's antioxidant defense system, encompassing sulfur allicin and phytochelatin metabolism, crucial for combating the phytotoxicity of PS and As. In summary, PS exerted a detrimental influence on garlic, exacerbating As toxicity. The findings from this study offer insights for subsequent investigations involving Liliaceae plants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite the acknowledged significance of nutrition in bone development, effects of methionine (Met) and cysteine (Cys) on bone quality remain under-researched, particularly during Eimeria challenge. We investigated the effects of different supplemental Met to Cys ratios (MCR) on bone quality of broilers under Eimeria challenge. A total of 720 fourteen-day old Cobb500 broilers were allocated into a 5 × 2 factorial arrangement. Five diets with Met and Cys supplemented at MCR of 100:0, 75:25, 50:50, 25:75, and 0:100 were fed to the birds with or without Eimeria challenge. Body composition was measured by dual energy x-ray absorptiometry, and the femur bone characteristics were assessed by microtomography. Data were analyzed by two-way ANOVA and orthogonal polynomial contrast. The results reaffirmed the detrimental effects of Eimeria challenge on bone quality. On 9 d post inoculation (DPI), significant interaction effects were found for whole body bone mineral content (BMC), lean tissue weight, and body weight (P < 0.05); in the nonchallenged group (NCG), these parameters linearly decreased as MCR decreased (P < 0.05). In the challenged group (CG), body weight and lean tissue weight were unaffected by MCR, and BMC linearly increased as MCR decreased (P < 0.05). For the cortical bone of femoral metaphysis on 6 DPI, bone mineral density (BMD) linearly increased as MCR decreased (P < 0.05). Bone volume to tissue volume ratio (BV/TV) in the CG linearly increased as MCR decreased (P < 0.05). On 9 DPI, BMC and TV linearly increased as MCR decreased (P < 0.05) in the NCG. BMD and BV/TV changed quadratically as MCR decreased (P < 0.05). For the trabecular bone of femoral metaphysis on 9 DPI, BV/TV, and trabecular number linearly increased as MCR decreased (P < 0.05) in the NCG. For the femoral diaphysis, BV, TV, BMC on 6 DPI, and BMD on 9 DPI linearly increased as MCR decreased (P < 0.05). In conclusion, this study showed that both Eimeria challenge and varying supplemental MCR could influence bone quality of broilers., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)